Biomarkers in Neural Disorders

Completed

• Conditions: Alzheimer's Disease; Progressive Supranuclear Palsy; Myasthenia Gravis; Spinal Cord Injuries; Diffuse Lewy Body Disease; Multiple System Atrophy; Essential Tremor; Parkinson's Disease; Drug Induced Parkinson's Disease
• Interventions: Other: Electrical Brainstem Responses; Other: Olfactory Tests; Other: Visual Deprivation; Other: Peripheral Nerve Stimulation

• Registration Number: NCT02761707
• Lead Sponsor: University of Pennsylvania

Brief Summary

This study seeks to establish the sensitivity and specificity of what appears to be a unique brainstem biomarker of Parkinson's Disease (PD) - an electrically induced olygosynaptic nasotrigeminal reflex response - in differentiating early stage PD from normal controls and from patients with various other neurodegenerative diseases. This study will additionally compare the biomarker to olfactory testing.

Detailed Description

Parkinson's disease (PD), a devastating age-related disease that is clinically defined by its effects on the motor system, afflicts more than six million people worldwide, imposing enormous burdens on patients, relatives, caretakers, and society in general. Diagnostic errors are common, particularly as symptoms first arise. The most common misdiagnoses are Alzheimer's disease (AD), essential tremor, and vascular pseudo-Parkinson's Disease. An accurate diagnosis is typically made at a later stage of the disease when marked and irreversible damage has occurred within the motor control system of the brain. Sensitive and specific biomarkers of the early stages of PD are urgently needed. Identification of such markers is critical for the development and assessment of medications and other interventions designed to eliminate or reduce the gradual and irreversible decline of neurons involved in the disorder. This study seeks to establish the sensitivity and specificity of what appears to be a unique brainstem biomarker of PD - an electrically induced trigeminal nerve blink reflex response - in differentiation of early stage PD from normal controls and such neurodegenerative diseases as early stage AD, progressive supranuclear palsy (PSP), and diffuse Lewy Body disease (DLBD). This study will additionally compare the biomarker to olfactory test results.

Study Timeline

• Study First Submitted: 2016-04-18
• Study First Submitted QC: 2016-05-03
• Study First Posted: 2016-05-04
• Study Start: 2016-06
• Primary Completion: 2018-06
• Status Verified: 2019-07
• Study Completion: 2019-07-16
• Last Update Submitted: 2019-07-16
• Last Update Posted: 2019-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• The Parkinson's disease (PD) patients will be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.
• The Alzheimer's disease (AD) patients will meet the 2011 National Institute on Aging-Alzheimer's Association and the 1984 National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association criteria for probable AD.
• The progressive supranuclear palsy (PSP) patients will have met the NINDS-SPSP criteria for probable PSP, which requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as a number of other clinical features.
• The DLBD patients will meet the Consensus Criteria for the clinical diagnosis of DLBD.
• The healthy controls will be matched to the PD patients on such variables as sex, age, education level, and ethnicity.
• The essential tremor (ET), multiple system atrophy (MSA), myasthenia gravis (MG), multiple system atrophy (MSA), Parkinson's disease dementia (D-PD), and Spinal Cord Injury (SCI) patients will meet the generally-accepted diagnostic criteria for these disorders.

Read More

Exclusion Criteria

• Drug abuse.
• Any other known and potentially confounding condition that could reasonably be expected to interfere with the study assessments.
• Under age 18.
• Over age 80.
• Smoker.
• Pregnant or nursing.
• Healthy control with a first degree relative who has a neurodegenerative disease.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Parkinson's Disease	Visual Deprivation	Non-smokers, ages 18-80, diagnosed with Parkinson's Disease. Must be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.
Spinal Cord Injury	Peripheral Nerve Stimulation	-
Parkinson's Disease	Electrical Brainstem Responses	Non-smokers, ages 18-80, diagnosed with Parkinson's Disease. Must be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.
Parkinson's Disease	Olfactory Tests	Non-smokers, ages 18-80, diagnosed with Parkinson's Disease. Must be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.
Parkinson's Disease	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, diagnosed with Parkinson's Disease. Must be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.
Alzheimer's Disease	Electrical Brainstem Responses	Non-smokers, ages 18-80, diagnosed with Alzheimer's Disease. Must meet the 2011 National Institute on Aging-Alzheimer's Association and the 1984 National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association criteria for probable AD.
Progressive Supranuclear Palsy	Electrical Brainstem Responses	Non-smokers, ages 18-80, diagnosed with Progressive Supranuclear Palsy. Must meet the NINDS-SPSP criteria for probable PSP, which requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as a number of other clinical features.
Essential Tremor	Electrical Brainstem Responses	Non-smokers, ages 18-80, diagnosed with Essential Tremor.
Alzheimer's Disease	Olfactory Tests	Non-smokers, ages 18-80, diagnosed with Alzheimer's Disease. Must meet the 2011 National Institute on Aging-Alzheimer's Association and the 1984 National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association criteria for probable AD.
Alzheimer's Disease	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, diagnosed with Alzheimer's Disease. Must meet the 2011 National Institute on Aging-Alzheimer's Association and the 1984 National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association criteria for probable AD.
Progressive Supranuclear Palsy	Olfactory Tests	Non-smokers, ages 18-80, diagnosed with Progressive Supranuclear Palsy. Must meet the NINDS-SPSP criteria for probable PSP, which requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as a number of other clinical features.
Essential Tremor	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, diagnosed with Essential Tremor.
Progressive Supranuclear Palsy	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, diagnosed with Progressive Supranuclear Palsy. Must meet the NINDS-SPSP criteria for probable PSP, which requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as a number of other clinical features.
Drug-Induced Parkinson's Disease	Electrical Brainstem Responses	Non-smokers, ages 18-80, diagnosed with Drug-Induced Parkinson's Disease.
Drug-Induced Parkinson's Disease	Olfactory Tests	Non-smokers, ages 18-80, diagnosed with Drug-Induced Parkinson's Disease.
Healthy Controls	Visual Deprivation	Non-smokers, ages 18-80, with no neurodegenerative disease, and no first-degree relatives with a neurodegenerative disease.
Spinal Cord Injury	Olfactory Tests	-
Essential Tremor	Olfactory Tests	Non-smokers, ages 18-80, diagnosed with Essential Tremor.
Multiple System Atrophy	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, who have been diagnosed with Multiple System Atrophy.
Diffuse Lewy Body Disease	Olfactory Tests	Non-smokers, ages 18-80, diagnosed with Diffuse Lewy Body Disease. Must meet the Consensus Criteria for the clinical diagnosis of DLBD.
Asymptomatic Relatives	Electrical Brainstem Responses	-
Drug-Induced Parkinson's Disease	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, diagnosed with Drug-Induced Parkinson's Disease.
Multiple System Atrophy	Electrical Brainstem Responses	Non-smokers, ages 18-80, who have been diagnosed with Multiple System Atrophy.
Diffuse Lewy Body Disease	Electrical Brainstem Responses	Non-smokers, ages 18-80, diagnosed with Diffuse Lewy Body Disease. Must meet the Consensus Criteria for the clinical diagnosis of DLBD.
Diffuse Lewy Body Disease	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, diagnosed with Diffuse Lewy Body Disease. Must meet the Consensus Criteria for the clinical diagnosis of DLBD.
Healthy Controls	Olfactory Tests	Non-smokers, ages 18-80, with no neurodegenerative disease, and no first-degree relatives with a neurodegenerative disease.
Spinal Cord Injury	Electrical Brainstem Responses	-
Asymptomatic Relatives	Peripheral Nerve Stimulation	-
Myasthenia Gravis	Electrical Brainstem Responses	Non-smokers, ages 18-80, diagnosed with Myasthenia Gravis.
Myasthenia Gravis	Olfactory Tests	Non-smokers, ages 18-80, diagnosed with Myasthenia Gravis.
Myasthenia Gravis	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, diagnosed with Myasthenia Gravis.
Multiple System Atrophy	Olfactory Tests	Non-smokers, ages 18-80, who have been diagnosed with Multiple System Atrophy.
Healthy Controls	Electrical Brainstem Responses	Non-smokers, ages 18-80, with no neurodegenerative disease, and no first-degree relatives with a neurodegenerative disease.
Healthy Controls	Peripheral Nerve Stimulation	Non-smokers, ages 18-80, with no neurodegenerative disease, and no first-degree relatives with a neurodegenerative disease.
Asymptomatic Relatives	Olfactory Tests	-

Primary Outcome Measures

Name	Time	Method
Score on the Odor Discrimination/Memory Test	30 Minutes	The number of correct responses in picking out an odor previously presented from three foils 10, 30, and 60 sec later using the standardized Odor Detection/Discrimination Test (before and after short-term visual deprivation).
Latency, amplitude, and area under the curve of brainstem reflex response	1 Hour	Latency, amplitude, and area under the curve of electrical brainstem reflex response of trigeminal nerve branches measured on the face musculature (before and after short-term visual deprivation).
Score on an Odor Detection Threshold Test	20 Minutes	The average of 7 reversals in a staircase odor detection threshold test that employs phenyl ethyl alcohol (rose oil) concentrations ranging from -7 to -2 log dilutions in light mineral oil.
Score on the University of Pennsylvania Smell Identification Test	20 Minutes	The number of correct odor identification responses out of 40 from the standardized University of Pennsylvania Smell Identification Test (before and after short-term visual deprivation).

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States